GDC-046 is a potent, active and selective TYK2 antagonist (inhibitor) with Ki of 4.8, 0.7, 0.7 and 0.4 nM for TYK2, JAK1, JAK2 and JAK3 respectively.

Physicochemical Properties

Molecular Formula	C16H13CL2N3O2
Molecular Weight	350.199
Exact Mass	349.038
CAS #	1258292-64-6
PubChem CID	49839561
Appearance	Off-white to yellow solid powder
Density	1.5±0.1 g/cm3
Boiling Point	518.0±50.0 °C at 760 mmHg
Flash Point	267.1±30.1 °C
Vapour Pressure	0.0±1.3 mmHg at 25°C
Index of Refraction	1.721
LogP	3.12
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	23
Complexity	449
Defined Atom Stereocenter Count	0
InChi Key	IAFNAEGXTKTGHN-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H13Cl2N3O2/c17-11-2-1-3-12(18)14(11)16(23)20-10-6-7-19-13(8-10)21-15(22)9-4-5-9/h1-3,6-9H,4-5H2,(H2,19,20,21,22,23)
Chemical Name	2,6-dichloro-N-[2-(cyclopropanecarbonylamino)pyridin-4-yl]benzamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	GDC-046 exhibited a moderate level of potency in IL-12 pathway blocking (IL-12 pSTAT4 EC50=380 nM) in assays involving cells; however, it was less effective in IL and blocked the EPO (JAK2) pathway (EPO pSTAT5 EC50=1700 nM). -6 (JAK1) pathway (EC50=2000 nM for IL-6 pSTAT3)[1].
ln Vivo	In mice, GDC-046 displayed relatively high clearance (65 mL/min/kg) when injected intravenously (iv 1 mg/kg) and demonstrated limited oral exposure (AUC=2.6 μM·h , 5 mg/kg orally) [1].
References	[1]. Lead Optimization of a 4-aminopyridine Benzamide Scaffold to Identify Potent, Selective, and Orally Bioavailable TYK2 Inhibitors. J Med Chem. 2013 Jun 13;56(11):4521-36.

Solubility Data

Solubility (In Vitro)

DMSO : ~62.5 mg/mL (~178.47 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.94 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8555 mL	14.2776 mL	28.5551 mL
	5 mM	0.5711 mL	2.8555 mL	5.7110 mL
	10 mM	0.2856 mL	1.4278 mL	2.8555 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.